Sepsis monitor

ABSTRACT

Sensors are attached to a living being so as to generate corresponding sensor signals. A monitor is in communications with the sensors so as to derive physiological parameters responsive to the sensor signals. Predetermined limits are applied to the physiological parameters. At least one indicator responsive to the physiological parameters and the predetermined limits signal the onset of a sepsis condition in the living being.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority benefit under 35 U.S.C. §119(e)to U.S. Provisional Patent Application Ser. No. 60/800,629, filed May15, 2006, entitled “Septic Shock Monitor,” incorporated herein byreference.

BACKGROUND OF THE INVENTION

Sepsis is a serious medical condition caused by the body's response toan infection. The source of the infection can be any of a number ofplaces throughout the body. Bacterial infections are the most commoncause of sepsis, but sepsis can also be caused by fungal, parasitic, orviral infections. Toxins produced by an untreated or inadequatelytreated infection circulate in the bloodstream causing damage, forexample, to the brain, heart, lungs, kidneys and liver. Severe sepsiscan result in septic shock, a medical emergency in which the organs andtissues of the body are not receiving an adequate flow of blood.

SUMMARY OF THE INVENTION

The signs and symptoms of sepsis may be subtle. The unacceptably lowsurvival rate of severe sepsis indicates that current patientidentification strategies may be lacking. For example, conventionalpatient monitors give insufficient advance warning of deterioratingpatient health or the onset of potentially serious physiologicalconditions resulting from sepsis. Advantageously, a sepsis monitornoninvasively measures patient condition so as to provide caregiverswith an advanced warning or prediction of the onset sepsis. A sepsismonitor may also be configured to provide automatic intervention ortreatment of sepsis.

SIRS (systemic inflammatory response syndrome) refers to the systemicactivation of the body's immune response, such as from sepsis. SIRS ismanifested by, for example, the presence of more than one of atemperature greater than 38° C. or less than 36° C.; a heart rategreater than 90 beats/min.; and a respiration rate greater than 20breaths/min. Thus, in an embodiment, a sepsis monitor is responsive tomore than one of pulse rate, respiration rate and temperature.

Sepsis also results in large amounts of nitrous oxide (NO) released intothe blood. It has been shown that NO functions, in part, as a killermolecule that is activated by immune cells. The overproduction of NOduring sepsis induces excessive vascular relaxation and a profoundhypotension that is also a characteristic feature of sepsis. NOinteracts rapidly with hemoglobin to form methemoglobin (HbMet). Thus,HbMet can function as a marker for NO generation in patients withsepsis. Further, endogenously produced CO functions as a messengermolecule as part of a complex cascade of mediators resulting fromsepsis. A portion of the endogenous CO is exhaled and a portion ispresent as carboxyhemoglobin (HbCO). Thus, in an embodiment, a sepsismonitor is responsive to one or more of HbCO, HbMet and blood pressure.

In an embodiment, sepsis monitoring is based upon one or morephysiological parameters and associated parameter limits, trends,patterns and variability, alone or in combination. The physiologicalparameters may include: blood parameters derived from an optical sensorincluding one or more of oxygen saturation (SpO₂), pulse rate, HbCO andHbMet; respiration rate (RR) derived from an acoustic sensor or acapnography sensor, as examples; noninvasive blood pressure (NIBP)derived from a blood pressure sensor, such as an inflatable cuff andcorresponding acoustic sensor, a continuous NIBP (CNIBP) measurementdevice or an intelligent cuff inflation (ICI) device, to name a few; andtemperature manually measured or derived from a thermistor or othertemperature transducer.

One aspect of a sepsis monitor is sensors attached to a living being soas to generate corresponding sensor signals. A monitor is incommunications with the sensors so as to derive physiological parametersresponsive to the sensor signals. Predetermined limits are applied tothe physiological parameters. At least one indicator responsive to thephysiological parameters and the predetermined limits signal the onsetof a sepsis condition in the living being.

Another aspect of a sepsis monitor is identifying physiologicalparameters indicative of an onset of a sepsis condition in a livingbeing. Sensor signals are generated that are responsive to thephysiological parameters. The physiological parameters are computed fromthe sensor signals. Predetermined rules are applied to the physiologicalparameters so as to determine the onset of the sepsis condition. Anindicator signals the potential existence and likely nonexistence of thesepsis condition.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a general block diagram of a sepsis monitoring system;

FIGS. 2A-B are detailed diagrams of sepsis monitoring systemembodiments;

FIG. 3 is an illustration of a sepsis monitoring system embodiment;

FIG. 4 is a general block diagram of a sepsis monitor incorporating amultiple parameter processor; and

FIG. 5 is a detailed block diagram of a multiple parameter processorembodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 illustrates a sepsis monitoring system 100 having one or moresensors 106 generating sensor signals 107 in response to physiologicalstates of a living being, such as a patient 1. A sepsis monitor 400processes the sensor signals 107 and generates sepsis indicators 102 orintervention controls 103 or both, in response. In an open-loopconfiguration, one or more sepsis indicators 102 are observed by acaregiver 2, who administers treatment in response. Alternatively, or inaddition, the caregiver 2 initiates, pauses, halts or adjusts thesettings of a sepsis treatment device 104 in response to the sepsisindicators 102. In an embodiment, the sepsis indicators 102 signal oneor more of a prediction of the onset of sepsis, a sepsis condition, aprediction of the onset of septic shock and a septic shock condition. Ina closed-loop configuration, the sepsis treatment device 104 isresponsive to one or more intervention controls 103 so as to affect thetreatment of the patient 1, including, for example, initiating, pausing,halting or adjusting the dosage of administered drugs. In an embodiment,the intervention controls 103 are responsive to one or more of aprediction of the onset of sepsis, a sepsis condition, a prediction ofthe onset of septic shock and a septic shock condition.

As shown in FIG. 1, the sepsis treatment device 104 may be a druginfusion device, a medical gas inhalation device or a ventilation deviceto name a few. Drug infusion device and gas inhalation device control isdescribed in U.S. patent application Ser. No. 11/654,904, filed Jan. 17,2007, entitled Drug Administration Controller and incorporated byreference herein. Closed loop respirator control is described in U.S.patent application Ser. No. 11/585,678, filed Oct. 23, 2006, entitledRobust Ventilator Control and incorporated by reference herein.

As shown in FIG. 1, sensors 106 provide noninvasive measurements andinclude, for example, an optical sensor attached to a tissue site, suchas a fingertip, for measuring one or more blood parameters. Noninvasivesensors 106 may also include acoustic sensors, blood pressure cuffs, ECGor EEG electrodes, CO₂ measuring capnography sensors and temperaturesensors to name but a few. The sepsis monitor 400 is responsive tosensors signals 107 so as to generate parameter measurements, which mayinclude SpO₂, pulse rate, perfusion index, perfusion variability index,HbCO, HbMet, total hemoglobin, fractional saturation, glucose, cyanide,respiration rate, blood pressure, CO₂, bilirubin, lung volume, cardiacoutput, temperature, consciousness and hydration measures, among otherparameters. Such parameters may be measured intermittently orcontinuously. Although sensors 106 are described above with respect tononinvasive technologies, sensors 106 may be invasive or noninvasive.Invasive measurements may require a person to prepare a blood or tissuesample, which is then processed by an instrument or testing device, withthe result read from the instrument or device and manually entered intothe sepsis monitor 400.

The sepsis monitor 400 may be a single instrument incorporating varioushardware, software, circuits and code for processing sensor signals,deriving physiological parameters and processing those parameters togenerate the indicators and controls described above. Alternatively, thesepsis monitor 400 may integrate one or more standalone instruments orplug-ins, each of which process specific sensor signals and deriveparticular physiological parameters. These may include blood parametermonitors, respiration rate monitors, blood pressure monitors, ECG andEEG monitors and capnometers, as a few examples.

In an embodiment, sensors 106 include a multiple wavelength opticalsensor, such as described in U.S. patent application Ser. No.11/376,013, filed Mar. 1, 2006 and entitled Multiple Wavelength SensorEmitters; and the sepsis monitor 400 incorporates a patient monitor,such as described in U.S. patent application Ser. No. 11/367,033, filedMar. 1, 2006 and entitled Noninvasive Multi-Parameter Patient Monitor,both patent applications assigned to Masimo Laboratories, Irvine, Calif.and both incorporated by reference herein.

In an embodiment, sensors 106 and measurement devices 108 includemultiple wavelength sensors and corresponding noninvasive bloodparameter monitors, such as Rainbow™ adhesive and reusable sensors andRAD-57™ and Radical-7™ monitors for measuring SpO₂, pulse rate,perfusion index, signal quality, HbCO and HbMet among other parameters.The Rainbow™ sensors and RAD-57™ and Radical-7™ monitors are availablefrom Masimo Corporation, Irvine, Calif. In an embodiment, sensors 106include a pulse oximetry sensor, such as described in U.S. Pat. No.5,782,757 entitled Low Noise Optical Probes and the sepsis monitor 400incorporates a pulse oximeter, such as described in U.S. Pat. No.5,632,272 entitled Signal Processing Apparatus, both assigned to MasimoCorporation, Irvine, Calif. and both incorporated by reference herein.In other embodiments, sensors 106 also include any of LNOP® adhesive orreusable sensors, SofTouch™ sensors, Hi-Fi Trauma™ or Blue™ sensor allavailable from Masimo Corporation, Irvine, Calif. Further, the sepsismonitor 400 may also include any of Radical®, SatShare™, Rad-9™, Rad-5™,Rad-5v™ or PPO+™ Masimo SET® pulse oximeters all available from MasimoCorporation, Irvine, Calif.

In another embodiment, the sepsis monitor 400 and the sepsis treatmentdevice 104 are incorporated within a single unit. For example, thesepsis monitor 400 and treatment device 104 may be incorporated within asingle housing, or the devices may be separately housed but physicallyand proximately connected.

FIGS. 2A-B illustrate sepsis monitoring system embodiments 200, 205. Asshown in FIG. 2A with respect to a system embodiment 200, a sepsismonitor 400 is in communications with an optical sensor 210 and anacoustic sensor 220 attached to a patient 1. An optical sensor processor230 generates pulsatile-blood related parameters, such as pulse rate(PR) 234, in response to optical sensor signals 212. An acoustic sensorprocessor 240 generates body-sound related parameters 244, such asrespiration rate (RR), in response to acoustic sensor signals 222. Atemperature parameter 295 is generated via a temperature sensor ormanually entered. A multiple parameter processor 500 processes theparameter measurements 234, 244, 295 alone or in combination andgenerates sepsis indicators and alarms 254 or drug administrationcontrols 256, or both, in response. An acoustic sensor is described inU.S. Pat. No. 6,661,161 entitled Piezoelectric Biological Sound Monitorwith Printed Circuit Board and a corresponding respirator rate monitoris described in International App. No. PCT/CA2005/000536 and Pub. No. WO2005/096931, filed Apr. 8, 2005, both applications incorporated byreference herein.

As shown in FIG. 2B with respect to a system embodiment 205, a sepsismonitor 400 is in communications with an optical sensor 210 and a NIBPsensor 260 attached to a patient 1. An optical sensor processor 230generates pulsatile-blood related parameters, such as such as HbCO 236and HbMet 238 in response to optical sensor signals 212. An NIPBprocessor 270 generates blood pressure (BP) parameters, in response toNIBP sensor signals 262. A multiple parameter processor 500 processesthe parameter measurements 236, 238, 274 alone or in combination andgenerates sepsis indicators and alarms 254 or drug adminstrationcontrols 256, or both, in response. A continuous NIBP (CNIBP) sensor andprocessor are described in U.S. Pat. No. 5,590,649 entitled Apparatusand Method for Measuring an Induced Perturbation to Determine BloodPressure and an intelligent cuff inflation (ICI) sensor and processorare described in U.S. Pat. No. 5,785,659 entitled AutomaticallyActivated Blood Pressure Measurement Device, both patents incorporatedby reference herein.

Advantageously, the multiple parameter processor 500 is responsive to acombination of multiple physiological parameters to indicate sepsis sothat an alert can be provided based upon these parameters. Further, themultiple parameter processor 500 responds not only to parameter limitsbut also to parameter trend information, parameter patterns andparameter variability, so as to reflect a patient condition over time.In an embodiment, sepsis indicators 254 include alarms and wellnessindicators that indicate stages of sepsis from none, to the onset ofsepsis, to severe sepsis and septic shock. These outputs, for example,provide a warning of a potential onset of sepsis at an early stage andcan trigger alarms as sepsis symptoms progress. Further, drugadministration control 256 controls the administration of drugs oralters drug doses in response to patient condition. In an embodiment,the multiple parameter processor 500 compares parameter limits andrising or falling trends of the measurements 234, 244,236, 238, 274, 295alone or in combination, with corresponding predetermined thresholds andgenerates indicators and alarms 254 or drug administration controls 256in response. The comparisons utilize a rule-based metric analysis, asdescribed in detail in respect to FIGS. 4-5, below.

In one embodiment, the sepsis indicators 254 include a green indicatorsignaling a stable condition, a yellow indicator signaling a less stablecondition or a potential sepsis onset and a red indicator signaling anunstable or severe sepsis condition. The indicators 254 may be, forexample, various display LEDs emitting wavelengths of the appropriatecolors. In an embodiment, a sepsis monitor 400 provides indicators 254according to TABLES 1 and 2 below.

In an embodiment according to TABLE 1, below, if a patient's pulse rate(PR) and respiration rate (RR) are less than predetermined maximumlimits and their body temperature is within a predetermined normalrange, then the sepsis monitor 400 displays a green indicator. However,if more than one of pulse rate, respiration rate and body temperatureare changing, where applicable changes in pulse rate and respirationrate are rate increases, then the sepsis monitor 400 displays a yellowindicator, signaling a potential onset of sepsis. If more than one ofpulse rate, respiration rate and temperature become abnormal, includingpulse rate and respiration rate above a predetermined limit andtemperature outside of a predetermined range, then the sepsis monitor400 displays a red indicator, signaling a potential sepsis condition.

TABLE 1 Rule-Based Monitor Outputs RULE OUTPUT If PR < heart rate limit;Then illuminate green  RR < breathing rate limit; & indicator.  T innormal range. If PR rising > heart rate trend limit; Then illuminateyellow  RR rising > breathing rate trend limit; & indicator  T rising orfalling. If PR > heart rate limit; Then illuminate red  RR > breathingrate limit; & indicator;  T outside normal range. Trigger audible alarm.

In an embodiment according to TABLE 2, below, if a patient'scarboxyhemoglobin (HbCO), methemeglobin (HbMet) and blood pressure (BP)are normal, i.e. HbCO and HbMet less than predetermined maximum limitsand BP greater than a predetermined minimum limit, then the sepsismonitor 400 displays a green indicator. However, if any of HbCO, HbMetand BP are changing, where applicable changes in HbCO and HbMet areincreases and the applicable change in BP is a decrease, then the sepsismonitor 400 displays a yellow indicator, signaling a potential onset ofsepsis. If any of HbCO, HbMet and BP change beyond predetermined limits,then the sepsis monitor 400 displays a red indicator, signaling apotential sepsis condition.

TABLE 2 Additional Rule-Based Monitor Outputs RULE OUTPUT If HbCO < COlimit; Then illuminate green indicator.  HbMet < Met limit; &  BP >blood pressure limit. If HbCO rising > CO trend limit; Then illuminateyellow indicator  HbMet rising > Met trend limit or  BP falling. IfHbCO > HbCO limit threshold; Then trigger an alarm, such as  HbMet >HbMet limit threshold; or an audible or a visual alert or  BP < bloodpressure limit. both.

In other embodiments, a sepsis monitor 400 utilizes predetermined limitsand ranges on any or all of PR, RR, T, HbCO, HbMet and BP to indicate nosepsis, a potential onset of sepsis or a sepsis condition, with green,yellow and red indicators or with other visual and audible indicators,displays and alarms. Other indicators, alarms, controls and diagnosticsin response to various combinations of parameters and thresholds can besubstituted for, or added to, the rule-based outputs illustrated inTABLES 1 and 2.

Other parameter measurements that may be input to the multiple parameterprocessor 500 include oxygen saturation (SpO₂) and perfusion index (PI)as derived from a pulse oximeter, ECG, EEG and ETCO₂, to name a few. Allof these parameters may indicate real-time measurements and historicaldata such as measurement trends, patterns and variability. Signalquality measurements may also be input to the multiple parameterprocessor 500. Pulse oximetry signal quality and data confidenceindicators are described in U.S. Pat. No. 6,684,090 entitled PulseOximetry Data Confidence Indicator, a pattern recognition alarmindicator is described in U.S. Pat. No. 6,822,564 entitled ParallelMeasurement Alarm Processor, both patents assigned to MasimoCorporation, Irvine, Calif. and incorporated by reference herein.

FIG. 3 illustrates a sepsis monitoring system 300 combining a sepsismonitor 400 (FIG. 1) and a drug administration device 204 (FIGS. 2A-B)into a drug infusion monitor 301. The sepsis monitoring system 300 hasan optical sensor 306 and a piezoelectric sensor 316 attached to apatient's body 1. The optical sensor 306 detects pulsatile bloodcomponents and the piezoelectric sensor 316 detects tracheal sounds. Thecorresponding optical and acoustic sensor signals are transmitted to thedrug infusion monitor 301 via an optical-sensor cable 307 and anacoustic-sensor cable 317. The drug infusion monitor 301 generates bloodparameter measurements such as PR, HbCO and HbMet and biological soundmeasurements such as respiration rate (RR) and processes themeasurements to display sepsis indicators and administer correspondingtreatments. In a particular embodiment, the drug infusion monitor 301intravenously administers one or more drugs, such as recombinantactivated protein C, to the patient 1 in doses and dose intervals so asto respond to varying stages of sepsis or the potential onset of sepsisand to transitions between less severe and more severe stages of sepsis.

FIG. 4 illustrates a sepsis monitor embodiment 400 having sensor signalprocessor(s) 401, a multiple parameter processor 500, sensor signalinputs 410 to the signal processor(s) 401 and monitor outputs 430 fromthe parameter processor 500. Monitor outputs 430 may be sepsis alarms,wellness indicators, controls and sepsis diagnostics. Alarms may be usedto alert medical personnel to a potential urgent or emergency medicalcondition in a patient under their care. Wellness indicators may be usedto inform medical personnel as to patient condition stability orinstability, such as a less urgent but potentially deteriorating medicalstate or condition. Diagnostics may be messages or other indicators usedto assist medical personnel in diagnosing or treating a patientcondition. Controls may be used to affect the operation of a medicaltreatment device, as described above, or other medical-relatedequipment.

In an embodiment, the multiple parameter processor 500 also has an inputand output port (I/O) 405 that provides communications to the outsideworld. The I/O includes user I/O and external device communications toname a few. User I/O allows manual data entry and control. For example,a menu-driven operator display may be provided to allow entry ofpredetermined alarm thresholds. External device communications mayinclude interfaces, networks or wireless communications to PCs,printers, chart recorders or displays to name a few.

FIG. 5 illustrates a sepsis monitor embodiment 500 having apre-processor 510, a metric analyzer 520, a post-processor 530 and acontroller 540. The pre-processor 510 has inputs 420 that may bereal-time physiological parameter measurements, historical physiologicalparameter measurements, signal quality measures or any combination ofthe above. The pre-processor 510 generates metrics 512 that may includehistorical or real-time parameter trends, detected parameter patterns,parameter variability measures and signal quality indicators to name afew. As examples, trend metrics may indicate if a physiologicalparameter is increasing or decreasing at a certain rate over a certaintime, pattern metrics may indicate if a parameter is cyclical within aparticular frequency range or over a particular time period, variabilitymetrics may indicate the extent of parameter stability.

As shown in FIG. 5, the metric analyzer 520 is configured to providetest results 522 to the post-processor based upon various rules appliedto the metrics 512 in view of various thresholds 524. As an example, themetric analyzer 520 may output an alarm trigger 522 to thepost-processor 530 when a parameter measurement 503 increases fasterthan a predetermined rate. This may be expressed, as an example, by arule that states “if trend metric exceeds trend threshold then triggeralarm.” TABLE 1 and TABLE 2, above, illustrate sepsis monitor rulesapplied to metrics including PR, RR, T, HbCO, HbMet and BP parametersand trends.

Also shown in FIG. 5, the post processor 530 inputs test results 522 andgenerates outputs 502 including alarms, wellness indictors, controls anddiagnostics. Alarms may be, for example, audible or visual alertswarning of critical conditions that need immediate attention. Wellnessindicators may be audible or visual cues, such as an intermittent,low-volume tone or a red/yellow/green light indicating a patient with astable or unstable physiological condition, as examples. Controls may beelectrical or electronic, wired or wireless or mechanical outputs, toname a few, capable of interfacing with and affecting another device.Diagnostics may indicate a particular patient condition, such as thepotential onset of sepsis.

Further shown in FIG. 5, the controller 540 interfaces with I/O 509. Inone embodiment, the I/O 509 provides predetermined thresholds, which thecontroller 540 transmits to the metric analyzer 520. The controller 540may also define metrics 514 for the pre-processor 510 and define outputs534 for the post-processor 530.

A sepsis monitor has been disclosed in detail in connection with variousembodiments. These embodiments are disclosed by way of examples only andare not to limit the scope of the claims that follow. One of ordinaryskill in art will appreciate many variations and modifications.

1. A sepsis monitor comprising: a plurality of sensors adapted to beattached to a living being so as to generate a corresponding pluralityof sensor signals, at least one of said sensors comprising an opticalsensor outputting a first signal of said at least one of said pluralityof sensor signals, said first signal indicative of a blood parameterincluding at least one of oxygen saturation, methemoglobin, orcarboxyhemoglobin; a monitor in communication with the sensors so as toderive a plurality of physiological parameters responsive to the sensorsignals, said parameters including at least one of methemoglobin orcarboxyhemoglobin responsive to said first signal, and to apply aplurality of predetermined limits to the physiological parametersassociated with sepsis; and at least one indicator responsive to themonitor's application of the predetermined limits to signal the onset ofa sepsis condition in the living being.
 2. The sepsis monitor accordingto claim 1 further comprising: a treatment device adapted to be attachedto the patient; and a control in communication with the treatmentdevice, wherein the control is responsive to the monitor so as tomoderate treatment provided by the treatment device to the living beingaccording to the sepsis condition.
 3. The sepsis monitor according toclaim 1 wherein the physiological parameters include at least two ofrespiration rate, pulse rate and temperature of the living being.
 4. Thesepsis monitor according to claim 1 wherein the physiological parametersinclude at least another of HbCO, HbMet, and blood pressure.
 5. Thesepsis monitor according to claim 2 wherein the treatment device is adrug administration device adapted to be intravenously connected to theliving being so as to administer at least one drug to the patient inresponse to the control.
 6. A method of electronically monitoringsignals indicative of a patient condition to determine when to warn acaregiver that said patient condition is indicative of sepsis, themethod comprising: outputting a first signal from a noninvasive opticalsensor indicative of an absorption of light by body tissue of saidpatient, said first signal also indicative of one or more physiologicalparameters of said patient; outputting a second signal from one of (i) anoninvasive acoustic sensor applied to an area of skin around apatient's throat where said second signal is indicative of acousticallysensed tracheal sounds or (ii) a noninvasive blood pressure cuff devicewhere said second signal is indicative of blood pressure; electronicallyprocessing with a processor said first signal to output measurementvalues for said one or more physiological parameters including at leastone of methemoglobin or carboxyhemoglobin and processing with saidprocessor said second signal to output measurement values for said oneof said respiration or said blood pressure; electronically applying withsaid processor a plurality of predetermined rules associated with sepsisto said measurement values; and when said application of said rulesindicates said patient condition is indicative of sepsis, outputting atleast one of an audio or visual indication to said caregiver that apotential for sepsis exists.
 7. The method according to claim 6, whereinthe outputting includes activating a first colored light to indicatenonexistence of said potential for said sepsis and a second coloredlight to indicate said potential of said sepsis.
 8. The method accordingto claim 6, further comprising sending a control signal to a drugadministration device intravenously in communications with said patient,said control signal responsive to said indication of said sepsis, saiddevice providing treatment for said sepsis.